Famciclovir (Page 4 of 9)
8.5 Geriatric Use
Of 816 patients with herpes zoster in clinical studies who were treated with famciclovir, 248 (30.4%) were greater than or equal to 65 years of age and 103 (13%) were greater than or equal to 75 years of age. No overall differences were observed in the incidence or types of adverse events between younger and older patients. Of 610 patients with recurrent herpes simplex (type 1 or type 2) in clinical studies who were treated with famciclovir, 26 (4.3%) were greater than 65 years of age and 7 (1.1%) were greater than 75 years of age. Clinical studies of famciclovir in patients with recurrent genital herpes did not include sufficient numbers of subjects aged 65 years and over to determine whether they respond differently compared to younger subjects.
No famciclovir dosage adjustment based on age is recommended unless renal function is impaired [see Dosage and Administration (2.3), Clinical Pharmacology (12.3)]. In general, appropriate caution should be exercised in the administration and monitoring of famciclovir in elderly patients reflecting the greater frequency of decreased renal function and concomitant use of other drugs.
8.6 Patients with Renal Impairment
Apparent plasma clearance, renal clearance, and the plasma-elimination rate constant of penciclovir decreased linearly with reductions in renal function. After the administration of a single 500 mg famciclovir oral dose (n=27) to healthy volunteers and to volunteers with varying degrees of renal impairment (CLCR ranged from 6.4 to 138.8 mL/min), the following results were obtained (Table 4):
| Table 4: Pharmacokinetic Parameters of Penciclovir in Subjects with Different Degrees of Renal Impairment | ||||
| Parameter (mean ± S.D.) | CLCR * ≥60 (mL/min) (n=15) | CLCR 40 to 59 (mL/min) (n=5) | CLCR 20 to 39 (mL/min) (n=4) | CLCR <20 (mL/min) (n=3) |
| CLCR (mL/min) | 88.1 ± 20.6 | 49.3 ± 5.9 | 26.5 ± 5.3 | 12.7 ± 5.9 |
| CLR (L/hr) | 30.1 ± 10.6 | 13 ± 1.3† | 4.2 ± 0.9 | 1.6 ± 1.0 |
| CL/F ‡ (L/hr) | 66.9 ± 27.5 | 27.3 ± 2.8 | 12.8 ± 1.3 | 5.8 ± 2.8 |
| Half-life (hr) | 2.3 ± 0.5 | 3.4 ± 0.7 | 6.2 ± 1.6 | 13.4 ± 10.2 |
In a multiple-dose study of famciclovir conducted in subjects with varying degrees of renal impairment (n=18), the pharmacokinetics of penciclovir were comparable to those after single doses.
A dosage adjustment is recommended for patients with renal impairment [see Dosage and Administration (2.3) ].
8.7 Patients with Hepatic Impairment
Mild or moderate hepatic impairment (chronic hepatitis [n=6], chronic ethanol abuse [n=8], or primary biliary cirrhosis [n=1]) had no effect on the extent of availability (AUC) of penciclovir following a single dose of 500 mg famciclovir. However, there was a 44% decrease in penciclovir mean maximum plasma concentration (Cmax ) and the time to maximum plasma concentration (tmax ) was increased by 0.75 hours in patients with hepatic impairment compared to normal volunteers. No dosage adjustment is recommended for patients with mild or moderate hepatic impairment. The pharmacokinetics of penciclovir has not been evaluated in patients with severe hepatic impairment. Conversion of famciclovir to the active metabolite penciclovir may be impaired in these patients resulting in a lower penciclovir plasma concentrations, and thus possibly a decrease of efficacy of famciclovir [see Clinical Pharmacology (12) ].
8.8 Black and African American Patients
In a randomized, double-blind, placebo-controlled trial conducted in 304 immunocompetent black and African American adults with recurrent genital herpes there was no difference in median time to healing between patients receiving famciclovir or placebo. In general, the adverse reaction profile was similar to that observed in other famciclovir clinical trials for adult patients [see Adverse Reactions (6.1) ]. The relevance of these study results to other indications in black and African American patients is unknown [see Clinical Studies (14.2) ].
10 OVERDOSAGE
Appropriate symptomatic and supportive therapy should be given. Penciclovir is removed by hemodialysis.
11 DESCRIPTION
Famciclovir Tablets contain famciclovir, USP, an orally administered prodrug of the antiviral agent penciclovir. Chemically, famciclovir, USP is known as 2-[2-(2-amino-9H -purin-9-yl)ethyl]-1,3-propanediol diacetate. It is a synthetic acyclic guanine derivative and has the following structure:
C14 H19 N5 O4 M.W. 321.3
Famciclovir, USP is a white to pale yellow solid. It is freely soluble in acetone and methanol, and sparingly soluble in ethanol and isopropanol. At 25°C famciclovir, USP is freely soluble (greater than 25% w/v) in water initially, but rapidly precipitates as the sparingly soluble (2% to 3% w/v) monohydrate. Famciclovir, USP is not hygroscopic below 85% relative humidity. Partition coefficients are: octanol/water (pH 4.8) P = 1.09 and octanol/phosphate buffer (pH 7.4) P = 2.08.
Each white, film-coated tablet contains famciclovir, USP. The 125 mg and 250 mg tablets are round; the 500 mg tablets are capsule-shaped. Inactive ingredients consist of croscarmellose sodium, hydroxypropyl cellulose, hypromellose, polydextrose, polyethylene glycol, silicified microcrystalline cellulose, sodium starch glycolate, sodium stearyl fumarate, titanium dioxide, and triacetin.
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